They would need ----(b)(4)--------------------------------- leukocyte-reduced labeling.

They need to add the times to the label (Lore has this in her memo).

Their ISBT labels are completely wrong and we will send them the reference for the information.

Ink/Labeling:

There was concern about when the extraction studies were done compared to when the bags were exposed to Citrate – the tox study may need to be repeated.

They need an extraction study on the leukocyte filter itself. CDRH evaluates these filters with the proper types of solvents. We may want to talk to them to see what is the proper extraction study for Hemerus to accurately access what can leach out of the filter. They were using water and that is probably not going to work.

The compliment assay and inactivated PTT assay were not done correctly.

The sponsor has not done implantation assays. ISO and USP 88 indicate that the bag can be cut into strips and implanted in a rat. The endpoints are edema, among other things, a few days later. -----------------------------------------(b)(4)-----------------------------------------------------------.

The final bag is likely identical to their bag cleared in 2008 via the 510(k) pathway.

Other product issues:

They refer to this as a device throughout their submission, so they need to remove this language as this is an NDA.

IFU had multiple issues. IFU do not describe a room temperature 8 hour hold RBC unit. IFU for clinical studies had instructions for the clinicians to do certain things in certain times and this was not in the IFU.

They do not say how they resolved the kinks in the tubing – which are known to cause hemolysis or cell activation.

In the JMS master file, they do not provide the source of the needle. They did not provide a BOM to tell you who they purchase this from, so it is unclear who the original suppliers are if they need to change. They do not list solvents used to anneal the filter.

Is there a push to put the particular type of plastic on the WB container to say DEHP or non-DEHP plastic? Perhaps CDER could address this.

They have a sample diversion pouch but have not done hemolysis studies for use of this pouch. In the past, we have seen these pouches cause hemolysis.

Does JMS, as the manufacturer of the bag and the anticoagulant, need to be listed on the label?

DMPQ- Sterilization

DMPQ will put together some questions for an IR about the sterilization cycle validations.

Design verification does not fall under DMPQ purview. Transportation, sterilization, and container closure is under our review.

PNR:Hemerus wants to call the whole system the The SOLX System.

The name should be listed in this order; the anticoagulant, the additive, and then the filter.

Action Items

1. Concurred, finalized Midcycle memos are due from the entire team by Thursday, April 5, 2012.

2. An information request (IR) /advice letter will be sent to Hemerus to include letter ready comments from the review memos.